Mechanical and Image-Based Assessments of Histotripsy and Tumor-Induced Changes in Osteosarcoma Tumor-Bearing Bone

Abstract

Osteosarcoma (OS) is a rare and aggressive bone cancer that often requires invasive limb-resection or limb-salvage surgery, which may lead to significant biomechanical challenges and an elevated risk of fracture. Histotripsy, a noninvasive focused ultrasound therapy, offers a promising alternative by selectively ablating tumor tissue while preserving surrounding structures. Although the safety and feasibility of OS tumor histotripsy ablation has already been demonstrated, its effects on the structural and mechanical integrity of OS-affected and healthy bone remain unknown. This knowledge is critical for advancing histotripsy as a safe, noninvasive limb-sparing strategy for OS. This dissertation developed predictive finite element (FE) models to evaluate the biomechanical effects of histotripsy on OS-affected bone through two aims. Aim 1 assessed histotripsy's impact on the structural and mechanical properties of OS-affected bone in an ex vivo canine model using mechanical testing and high resolution μCT imaging. Aim 2 investigated histotripsy's effects on whole-bone mechanics in an ex vivo murine model during tumor progression, integrating imaging data into FE models to predict fracture risk and evaluate treatment outcomes. The findings of this study establish critical data on the biomechanical effects of histotripsy on both healthy and diseased bone, advance predictive image-based FE modeling accuracy, and support the clinical translation of histotripsy as a noninvasive limb-salvage strategy for OS.